Project Summary/Abstract The hippocampus is a key structure in the study of weight regulation due to its implication in food motivation and intake. Although current research suggests that a state of obesity may lead to disruptions in hippocampal structure and hippocampal-dependent memory, a crucial question left unanswered is whether these differences could be observed in healthy-weight children prior to the onset of weight gain. Indeed, research shows that children with obesity (OB), compared to healthy-weight (HW) peers, have significantly reduced hippocampal volume. Moreover, there is evidence that OB children, relative to HW, have significantly poorer performances on hippocampal-dependent memory tasks. Thus, differences in hippocampal volume and memory may be attributed to a state of obesity and related factors (e.g., high consumption of a western diet, insulin resistance). However, an alternative hypothesis is that these differences are present prior to the onset of weight gain and acting as a risk factor for obesity. In fact, research in adults shows that adults at high-risk for obesity (HR), relative to low- risk for obesity (LR), show reduced total grey matter volume in several brain regions. Additionally, in women, grey matter volume reductions in the prefrontal cortex are associated with an increase in BMI over the following year. Thus, differences in neural structure may precede weight gain, and lead to an increased risk for obesity. However, examining whether these differences can be seen in children has not yet been evaluated. Further, it is necessary to examine whether differences are seen specifically in the hippocampus given that ample research shows associations of the hippocampus with obesity. Accordingly, this study will evaluate whether differences if hippocampal structure and hippocampal-dependent memory can be seen between HW children at high-risk for obesity (two overweight/obese parents), and those at low-risk for obesity (two healthy-weight parents). This ancillary study will utilize a sample of 132 HW, 8-11-year-old children at high-risk for obesity or low-risk for obesity recruited by the parent R01 (DK111106; Boutelle PI). Differences in hippocampal structure will be evaluated using magnetic resonance imaging (MRI) and differences in hippocampal-dependent memory will be evaluated using two subscales of the Child Memory Scale. Further, this study will examine the independent and additive relationships between hippocampal volume and functioning, and eating behaviors (i.e., eating in the absence of hunger, enjoyment of food and food responsiveness measured by the Child Eating Behavior Questionnaire, and reward-based eating), and whether these associations differ across risk groups (i.e., moderation effect of group). The ultimate goal for this proposal is to identify potential neurobiological and neuropsychological risk factors for weight gain and obesity in children. This knowledge will help identify children at a higher risk for weight gain and provide new targets for interventions to prevent obesity in youth.